IL-17介导巨噬细胞极化对BPA诱导肥胖中脂肪组织炎症的调控及机制研究

项目名称： IL-17介导巨噬细胞极化对BPA诱导肥胖中脂肪组织炎症的调控及机制研究

项目编号： No.81473015

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 沈彤

作者单位： 安徽医科大学

项目金额： 60万元

中文摘要： 双酚A（BPA）暴露诱导肥胖受到广泛关注，但其机制目前仍未完全阐明。文献提示调控肥胖发展的关键环节脂肪组织巨噬细胞（ATMs）极化可改变肥胖中脂肪组织炎症状态。本研究拟在课题组前期发现BPA促进巨噬细胞向M1型极化，及围生期BPA暴露引起子代血清IL-17水平升高的基础上，用IL-17中和抗体、IL-17基因敲除小鼠和IL-17+细胞过继转移，探讨脂肪组织激活IL-17+细胞，上调IL-17介导ATMs向M1型极化，加重脂肪组织ATMs聚集，促进脂肪组织炎症在BPA诱导肥胖中的作用；通过体外共培养实验验证BPA诱导肥胖中，BPA诱导脂肪细胞分化，脂肪组织脂肪细胞、IL-17+细胞和巨噬细胞相互作用，促进组织炎症，并结合RNA干扰实验深入研究IL-17调控ATMs极化的分子机制。本研究为阐明环境BPA暴露诱导肥胖的发病及调控机制提供新的科学依据，并为防治环境BPA暴露的健康危害提供新的思路。

中文关键词： 双酚A；IL-17；巨噬细胞；脂肪组织炎症；肥胖

英文摘要： Bisphenol A (BPA) is a ubiquitous environmental endocrine disrupting chemical. Recently, BPA -induced obesity attracted widespread attentions. However, the underlying mechanism has not yet been fully elucidated. Literature suggest that regulate the polarization of adipose tissue macrophages (ATMs) , the critical factor in development of obesity, can change the outcomes of obesity. Our previous studies have shown that BPA can promote macrophage polarization to the M1 type in vitro, as well as maternal exposure to low-dose BPA by drinking water during pregnancy and lactation, can lead to elevate serum IL-17 levels in offspring mice. On the basis of these results, this study intends to explore the activation of IL-17+ cells in adipose tissue, increase in IL-17 level, then mediate ATMs shift to M1-type polarization, aggravate the accumulation of macrophage in adipose tissue, contribute to adipose tissue inflammation in BPA-induced obesity, using IL-17 neutralizing antibody, IL-17 knockout mice and IL-17+ cells adoptive transfer experiments. In vitro, we cocultre various combinations of adipose tissue, IL-17+ cells and macrophages, to further explore the cellular interplay via which inflammation develops in obese adipose tissue of BPA-induced obesity.As well as, investigate the molecular mechanisms of IL-17 mediate the polarization of ATMs using RNA interference. The results of this study provide a new theoretical basis to elucidate the pathogenesis and regulator mechanisms of obesity induced by BPA exposure, and provide a new ideas for the prevention of health hazards of environmental BPA exposure.

英文关键词： Bisphenol A;IL-17;macrophage;adipose tissue inflammation;obesity